1-(5-'GH'-1H-indol-3-yl)propan-2-amine by Asch

Query Query

Results

Date

102 reactions in Reaxys

2016-08-15 16h:56m:07s (EST)

H 2N

1. Query

Search as: As drawn, No mixtures, No isotopes, No charges, No radicals

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E N O

NH 2

Rx-ID: 186739 View in Reaxys 1/102 Yield

Conditions & References

68 %

With lithium aluminium tetrahydride in tetrahydrofuran, Time= 12h, Inert atmosphere, Reflux Rodriguez-Mata, Maria; Gotor-Fernandez, Vicente; Gonzalez-Sabin, Javier; Rebolledo, Francisca; Gotor, Vicente; Organic and Biomolecular Chemistry; vol. 9; nb. 7; (2011); p. 2274 - 2278 View in Reaxys With lithium aluminium tetrahydride Young; Journal of the Chemical Society; (1958); p. 3493,3494 View in Reaxys Ash; Wragg; Journal of the Chemical Society; (1958); p. 3887,3892 View in Reaxys

N O

NH 2

Rx-ID: 2049181 View in Reaxys 2/102 Yield

Conditions & References

69 %

With nickel boride, hydrazine hydrate in isopropyl alcohol, Time= 0.5h, Heating Lloyd, David H.; Nicholas, David E.; Journal of Organic Chemistry; vol. 51; nb. 22; (1986); p. 4294 - 4295 View in Reaxys

NH 2

Rx-ID: 3627341 View in Reaxys 3/102 Yield

Conditions & References

87 %

With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH 2

Rx-ID: 3627342 View in Reaxys 4/102 Yield 87 %

Conditions & References With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr

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Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH 2

Rx-ID: 3627343 View in Reaxys 5/102 Yield

Conditions & References

94 %

With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH 2

Rx-ID: 3627344 View in Reaxys 6/102 Yield 94 %

Conditions & References With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH 2

Rx-ID: 5439262 View in Reaxys 7/102 Yield

Conditions & References aus II Bulatova; Suvorov; Pharmaceutical Chemistry Journal; vol. 2; nb. 2; (1968); p. 80 - 81 View in Reaxys IV, sd. 10percentig. HCl Terzian et al.; Experientia; vol. 17; (1961); p. 493; vol. 176 View in Reaxys α-Methyl-tryptamin-carbonsaeure-(2), wss. HCl <Δ> Suvorov,N.N. et al.; J. Gen. Chem. USSR (Engl. Transl.); vol. 32; nb. 5; (1962); p. 1567 - 1572,1552 - 1556 View in Reaxys Oxindol I, NaBH4/AlCl3 Patent; Parke, Davis + Co.; GB974894; (1961); ; vol. 62; nb. 9110a; (1965) View in Reaxys Oxindol I, LiAlH4

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Patent; Parke, Davis + Co.; GB974894; (1961); ; vol. 62; nb. 9110a; (1965) View in Reaxys 3-(2-Oximino-propyl)-indol, LiAlH4, THF Szmuszkovicz; Journal of Organic Chemistry; vol. 29; (1964); p. 843,845 View in Reaxys Indol IV Patent; Parke; Davis and Co.; GB974895; (1961); ; vol. 62; nb. 4009g; (1965) View in Reaxys 3-(2-Aminopropionyl)indol 1g, THF, LiAlH4 Bergman,J. et al.; Tetrahedron; vol. 29; (1973); p. 971 - 976 View in Reaxys 3-Hydroxy-3-(2-oximino-propyl)-oxindol, 2 taegige Red. mit NaBH4/AlCl3/2-Methoxy-ethylether bei 100grad Franklin; White; Journal of the Chemical Society; (1963); p. 1335,1336 View in Reaxys 3-Hydroxy-3-(2-oximino-propyl)-oxindol, besser Red. mit LiAlH4 in sd. THF Franklin; White; Journal of the Chemical Society; (1963); p. 1335,1336 View in Reaxys 3-(2-Nitro-2-methyl-ethylen)-indol, Erhitzen mit LiAlH4/THF Heinzelman et al.; Journal of Organic Chemistry; vol. 25; (1960); p. 1548,1552 View in Reaxys α-Methyl-β-indolenidenium-ethylnitronat, Erhitzen mit LiAlH4/Ae. Heinzelman et al.; Journal of Organic Chemistry; vol. 25; (1960); p. 1548,1552 View in Reaxys 3-Hydroxy-3-(2-oximino-propyl)-oxindol in THF, 1) LiAlH4 (20grad, dann Siedetemp., 12 Std.), 2) AlCl3/Ae. (100grad, 48 Std.), 3) wss. NaOH Franklin; White; Journal of the Chemical Society; (1963); p. 1335,1336 View in Reaxys 3-Hydroxy-3-(2-oximino-propyl)-oxindol in Bis-(2-methoxy-ethyl)-ether, 1) NaBH4 (20grad) 2) AlCl3/Ae. (100grad, 48 Std.), 3) wss. NaOH Franklin; White; Journal of the Chemical Society; (1963); p. 1335,1336 View in Reaxys 2 Patent; NOVARTIS AG; US2009/275560; (2009); (A1) English View in Reaxys

(+-)-3-<2-hydroxyimino-propyl>-indolin-2-one NH 2

Rx-ID: 5439263 View in Reaxys 8/102 Yield

Conditions & References With propan-1-ol, sodium Pietra; Tacconi; Farmaco, Edizione Scientifica; vol. 13; (1958); p. 893,907 View in Reaxys

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(+-)-3-<2-nitro-propyl>-indole NH 2

Rx-ID: 5439264 View in Reaxys 9/102 Yield

Conditions & References With ethanol, nickel, platinum, Hydrogenation Snyder; Katz; Journal of the American Chemical Society; vol. 69; (1947); p. 3140 View in Reaxys

NH 2

Rx-ID: 18815679 View in Reaxys 10/102 Yield

Conditions & References

57 %

With formate dehydrogenase, (S)-2-aminopropanoic acid, L-alanine dehydrogenase, (S)-selective transaminase from Silibacter pomeroyi, ammonium formate in aq. phosphate buffer, dimethyl sulfoxide, Time= 48h, T= 30 °C , Enzymatic reaction Fischereder, Eva-Maria; Pressnitz, Desiree; Kroutil, Wolfgang; ACS Catalysis; vol. 6; nb. 1; (2016); p. 23 - 30 View in Reaxys Reaction Steps: 2 1: 54 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 87 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 2 1: 19 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 87 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH 2

Rx-ID: 18815680 View in Reaxys 11/102 Yield 51 %

Conditions & References With formate dehydrogenase, D-Alanine, L-alanine dehydrogenase, (R)-selective transaminasefrom Arthrobacter sp., ammonium formate in aq. phosphate buffer, dimethyl sulfoxide, Time= 48h, T= 30 °C , Enzymatic reaction Fischereder, Eva-Maria; Pressnitz, Desiree; Kroutil, Wolfgang; ACS Catalysis; vol. 6; nb. 1; (2016); p. 23 - 30 View in Reaxys Reaction Steps: 2 1: 36 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 94 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol

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Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 2 1: 43 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 94 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH NH

N O

NH 2

Rx-ID: 18820698 View in Reaxys 12/102 Yield

Conditions & References Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 54 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 87 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 19 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 87 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH NH

N O

NH 2

Rx-ID: 18820699 View in Reaxys 13/102 Yield

Conditions & References Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 36 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 94 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 43 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 94 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr

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NH 2

Rx-ID: 22210998 View in Reaxys 14/102 Yield

Conditions & References Reaction Steps: 2 1: butylamine 2: LiAlH4 With lithium aluminium tetrahydride, N-butylamine Young; Journal of the Chemical Society; (1958); p. 3493,3494 View in Reaxys Reaction Steps: 2 1: benzylamine 2: LiAlH4 With lithium aluminium tetrahydride, benzylamine Ash; Wragg; Journal of the Chemical Society; (1958); p. 3887,3892 View in Reaxys Reaction Steps: 2 1: ammonium acetate / 6 h / Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / Inert atmosphere; Reflux With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran, 1: Henry reaction Rodriguez-Mata, Maria; Gotor-Fernandez, Vicente; Gonzalez-Sabin, Javier; Rebolledo, Francisca; Gotor, Vicente; Organic and Biomolecular Chemistry; vol. 9; nb. 7; (2011); p. 2274 - 2278 View in Reaxys Reaction Steps: 2 1: ammonium acetate / acetic acid / 8 h / 110 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 6 h / Reflux With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran, acetic acid Robaa, Dina; Enzensperger, Christoph; Eldin Abulazm, Shams; Hefnawy, Mohamed M.; El-Subbagh, Hussein I.; Wani, Tanveer A.; Lehmann, Jochen; Journal of Medicinal Chemistry; vol. 54; nb. 20; (2011); p. 7422 - 7426 View in Reaxys Reaction Steps: 2 1: piperidine; acetic acid / benzene / Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / Reflux With piperidine, lithium aluminium tetrahydride, acetic acid in tetrahydrofuran, benzene Nirogi, Ramakrishna V.S.; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P.; Shinde, Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys Reaction Steps: 2 1: ammonium acetate / 18 h / |Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 18 h / |Reflux With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran

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Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.; Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.; Bioorg. Med. Chem. Lett.; vol. 24; nb. 19; (2014); p. 4754 - 4758 View in Reaxys Reaction Steps: 2 1: ammonium acetate / 2 h / |Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 36 h / 0 - 20 °C / |Inert atmosphere With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran Zhao, Xiaohu; Liu, Xiaohua; Mei, Hongjiang; Guo, Jing; Lin, Lili; Feng, Xiaoming; Angewandte Chemie - International Edition; vol. 54; nb. 13; (2015); p. 4032 - 4035; Angew. Chem.; vol. 127; nb. 13; (2015); p. 4104 - 4107,4 View in Reaxys

H 2N

NH 2

Rx-ID: 23922933 View in Reaxys 15/102 Yield

Conditions & References 14 : Preparation of (S)-2-(1H-Indol-3-yl)-1-methylethylamine EXAMPLE 14 Preparation of (S)-2-(1H-Indol-3-yl)-1-methylethylamine A solution of (S)-2-amino-1-(1H-indol-3-yl)-propan-1-one (0.47 g, 2.5 mmol, 1.0 eq.) in acetonitrile and isopropanol is treated portionwise with NaBH4 (285 mg, 7.49 mmol, 3.0 equiv.), heated at reflux temperature for 24 h, stirred at room temperature under N2 for 36 h, quenched with methanol, concentrated and partitioned between water and EtOAc. The EtOAc phase is dried over MgSO4 and concentrated in vacuo to afford the title product as a brown oil, identified by HPLC and mass spectral analyses. With sodium tetrahydroborate in isopropyl alcohol, acetonitrile Patent; Wyeth; US2003/171353; (2003); (A1) English View in Reaxys

fumarate of (2R,1'S)-1-(2-(indol-3-yl)-1-methylethylamino)-3-(2methylphenoxy)propan-2-ol NH 2

Rx-ID: 25138560 View in Reaxys 16/102 Yield 30%

Conditions & References 1 : Neutral fumarate of (2R,1'S)-1-(2-(indol-3-yl)-1-methylethylamino)-3-(2-methylphenoxy)propan-2-ol (SR 41 583 A) Neutral fumarate of (2R,1'S)-1-(2-(indol-3-yl)-1-methylethylamino)-3-(2-methylphenoxy)propan-2-ol (SR 41 583 A) Using the method described above, this compound is obtained from 5.2 g of (S)(+)-α-methyltryptamine and g of (S) (+)-3-(2-methylphenoxymethyl)-1-tosyloxypropan-2-ol. The fumaric acid salt is formed in 45 ml of an ethyl acetate/methanol mixture (2/1; v/v), this being followed by crystallization from ethanol. 1.75 g of the expected compound are obtained. Yield: 30percent; M.p.=169°-170° C.; αD =+31.4 (c=1; ethanol/water:6/4; v/v); Optical rotation measured in polarized light at 400 nm=+81.4 (c=1; ethanol/water: 6/4; v/v). C23 H28 N2 O4: Analysis: Calculated: C=69.68 H=7.12 N=7.06. Found: C=69.89 H=7.06 N=6.97. Patent; Societe Anonyme: Sanofi; US4806655; (1989); (A1) English View in Reaxys

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fumarate of (2S)-1-(2-(indol-3-yl)-1-methylethylamino)-3-(2methylphenoxy)propan-2-ol NH 2

Rx-ID: 25186636 View in Reaxys 17/102 Yield

Conditions & References

20%

1.a : (a) The solid obtained is crystallized by dissolution in methylene chloride followed by the addition of isopropyl ether. This gives 8 g of (S)(+)-α-methyltryptamine. Yield: 20percent; M.p.=122°-123.5° C.; αD =+43.2 (c=1.05; absolute ethanol). C11 H14 N2: Analysis: Calculated: C=76.26 H=7.57 N=16.17. Found: C=75.56 H=8.11 N=15.44. in dichloromethane Patent; Societe Anonyme: Sanofi; US4806655; (1989); (A1) English View in Reaxys

O O

H N 2 H

NH 2

Rx-ID: 25201780 View in Reaxys 18/102 Yield

Conditions & References 1.b : (b) (b) (R)(-)-α-Methyltryptamine 25.6 g of d,l-α-methyltryptamine enriched in the (R)(-) epimer are recovered from the mother liquors obtained in the previous step, after treatment with sodium hydroxide. This compound is salified with 58 g of O,O'-bis-p-toluoyltartaric acid. The salt obtained is recrystallized 3 times from 900 ml of an ethanol/water mixture (2/1; v/v). 31 g of salt are isolated in this way and are then recrystallized by dissolution in methylene chloride followed by the addition of isopropyl ether. With sodium hydroxide in ethanol Patent; Societe Anonyme: Sanofi; US4806655; (1989); (A1) English View in Reaxys

O O HN

NH 2

Rx-ID: 28800481 View in Reaxys 19/102 Yield 80 %

Conditions & References F.3 :Step 3: The tosylate intermediate (580 mg, 1.21 mmol) is dissolved in 36 mL absolute ethanol and 72.7 mg palladium (II) hydroxide catalyst is added. The reaction mixture is stirred under 1 atm H2 atmosphere at room temperature for 2 hours. The reaction mixture is filtered through celite and the filtration is concentrated in vacuo. The residue

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is dissolved in EtOAc (50 mL), washed with sat aq NaHCO3 (50 mL, dried with magnesium sulfate, filtered and concentrated in vacuo to yield the S-amine (169 mg, 80percent). With hydrogen, palladium(II) oxide hydrate in ethanol, Time= 2h, T= 20 °C Patent; NOVARTIS AG; US2009/275560; (2009); (A1) English View in Reaxys 80 %

With hydrogen, palladium(II) oxide hydrate in ethanol, Time= 2h, T= 20 °C , p= 760.051Torr Yeung, Bryan K. S.; Zou, Bin; Rottmann, Matthias; Lakshminarayana, Suresh B.; Ang, Shi Hua; Leong, Seh Yong; Tan, Jocelyn; Wong, Josephine; Keller-Maerki, Sonja; Fischli, Christoph; Goh, Anne; Schmitt, Esther K.; Krastel, Philipp; Francotte, Eric; Kuhen, Kelli; Plouffe, David; Henson, Kerstin; Wagner, Trixie; Winzeler, Elizabeth A.; Petersen, Frank; Brun, Reto; Dartois, Veronique; Diagana, Thierry T.; Keller, Thomas H.; Journal of Medicinal Chemistry; vol. 53; nb. 14; (2010); p. 5155 - 5164 View in Reaxys

O O

S O

O HN O NH

NH 2

Rx-ID: 29626251 View in Reaxys 20/102 Yield

Conditions & References With hydrogen, palladium(II) oxide hydrate in ethanol, Time= 2h, T= 20 °C , p= 760.051Torr Yeung, Bryan K. S.; Zou, Bin; Rottmann, Matthias; Lakshminarayana, Suresh B.; Ang, Shi Hua; Leong, Seh Yong; Tan, Jocelyn; Wong, Josephine; Keller-Maerki, Sonja; Fischli, Christoph; Goh, Anne; Schmitt, Esther K.; Krastel, Philipp; Francotte, Eric; Kuhen, Kelli; Plouffe, David; Henson, Kerstin; Wagner, Trixie; Winzeler, Elizabeth A.; Petersen, Frank; Brun, Reto; Dartois, Veronique; Diagana, Thierry T.; Keller, Thomas H.; Journal of Medicinal Chemistry; vol. 53; nb. 14; (2010); p. 5155 - 5164 View in Reaxys O N

NH 2

Rx-ID: 29626255 View in Reaxys 21/102 Yield 89 %

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Time= 6h, Reflux Robaa, Dina; Enzensperger, Christoph; Eldin Abulazm, Shams; Hefnawy, Mohamed M.; El-Subbagh, Hussein I.; Wani, Tanveer A.; Lehmann, Jochen; Journal of Medicinal Chemistry; vol. 54; nb. 20; (2011); p. 7422 - 7426 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Reflux Yeung, Bryan K. S.; Zou, Bin; Rottmann, Matthias; Lakshminarayana, Suresh B.; Ang, Shi Hua; Leong, Seh Yong; Tan, Jocelyn; Wong, Josephine; Keller-Maerki, Sonja; Fischli, Christoph; Goh, Anne; Schmitt, Esther K.; Krastel, Philipp; Francotte, Eric; Kuhen, Kelli; Plouffe, David; Henson, Kerstin; Wagner, Trixie; Winzeler, Elizabeth A.; Petersen, Frank; Brun, Reto; Dartois, Veronique; Diagana, Thierry T.; Keller, Thomas H.; Journal of Medicinal Chemistry; vol. 53; nb. 14; (2010); p. 5155 - 5164 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Reflux

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Nirogi, Ramakrishna V.S.; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P.; Shinde, Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys General procedure: 1-(5’-Chloroindolyl)-2-nitro-1-butene (0.72 g, 2.8 mmol) was dissolved into anhydrous THF (9 mL). A solution of lithium aluminum hydride (1.0 M/THF, 9 mL, 9 mmol) was added slowly and the reaction was refluxed for 18 h. Upon cooling to room temperature, the reaction mixture was quenched with 1/1 water/THF and then basified to pH 0f 9 with 3.0 N aqueous NaOH solution. The mixture was filtered through Celite and the filtrate was concentrated to 0.73 g of brown oil. The crude material was purified by automated flash chromatography (silica gel, 20percent MeOH/DCM) to yield 0.3 g (47 percent) of colorless oil. This material was dissolved into diethyl ether (25 mL) and a solution of fumaric acid (0.17 g, (1.46 mmol) in MeOH (4 mL) was slowly added. The reaction stirred 18 h at room temperature and the solid product was filtered and recrystallized from MeOH/ethyl ether to yield 180 mg (45percent) of 7e as a white solid; With lithium aluminium tetrahydride in tetrahydrofuran, Time= 18h, Reflux Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.; Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.; Bioorg. Med. Chem. Lett.; vol. 24; nb. 19; (2014); p. 4754 - 4758 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Time= 36h, T= 0 - 20 °C , Inert atmosphere Zhao, Xiaohu; Liu, Xiaohua; Mei, Hongjiang; Guo, Jing; Lin, Lili; Feng, Xiaoming; Angewandte Chemie - International Edition; vol. 54; nb. 13; (2015); p. 4032 - 4035; Angew. Chem.; vol. 127; nb. 13; (2015); p. 4104 - 4107,4 View in Reaxys

NH NH

NH 2

Rx-ID: 39059101 View in Reaxys 22/102 Yield

Conditions & References Reaction Steps: 3 1.1: trichlorophosphate / 0.17 h / 20 °C 1.2: 1.25 h / 20 °C 1.3: 0.13 h / 100 °C 2.1: ammonium acetate / 18 h / |Reflux 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 18 h / |Reflux With lithium aluminium tetrahydride, ammonium acetate, trichlorophosphate in tetrahydrofuran Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.; Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.; Bioorg. Med. Chem. Lett.; vol. 24; nb. 19; (2014); p. 4754 - 4758 View in Reaxys

E N O

NH 2

Rx-ID: 265288 View in Reaxys 23/102 Yield

Conditions & References With lithium aluminium tetrahydride Young; Journal of the Chemical Society; (1958); p. 3493,3494 View in Reaxys

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NH 2

Rx-ID: 22211558 View in Reaxys 24/102 Yield

Conditions & References Reaction Steps: 2 1: ammonium acetate 2: LiAlH4 With ammonium acetate, lithium aluminium tetrahydride Young; Journal of the Chemical Society; (1958); p. 3493,3494 View in Reaxys

NH NH

NH 2

Rx-ID: 22221521 View in Reaxys 25/102 Yield

Conditions & References Reaction Steps: 3 1: phosphoryl chloride / anschliessend mit wss.Natronlauge 2: ammonium acetate 3: LiAlH4 With ammonium acetate, lithium aluminium tetrahydride, trichlorophosphate Young; Journal of the Chemical Society; (1958); p. 3493,3494 View in Reaxys

O NH 2

N H

Rx-ID: 41994284 View in Reaxys 26/102 Yield

Conditions & References

31 %

With formate dehydrogenase, D-Alanine, L-alanine dehydrogenase, (R)-selective transaminasefrom Arthrobacter sp., ammonium formate in aq. phosphate buffer, dimethyl sulfoxide, Time= 48h, T= 30 °C , Enzymatic reaction, stereoselective reaction Fischereder, Eva-Maria; Pressnitz, Desiree; Kroutil, Wolfgang; ACS Catalysis; vol. 6; nb. 1; (2016); p. 23 - 30 View in Reaxys

O NH 2

N H

Rx-ID: 41994285 View in Reaxys 27/102 Yield 30 %

Conditions & References With formate dehydrogenase, (S)-2-aminopropanoic acid, L-alanine dehydrogenase, transaminase from Bacillus megaterium, ammonium formate in aq. phosphate buffer, dimethyl sulfoxide, Time= 48h, T= 30 °C , Enzymatic reaction Fischereder, Eva-Maria; Pressnitz, Desiree; Kroutil, Wolfgang; ACS Catalysis; vol. 6; nb. 1; (2016); p. 23 - 30 View in Reaxys

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NH 2

Rx-ID: 2156675 View in Reaxys 28/102 Yield

Conditions & References With hydrogen, palladium on activated charcoal in ethanol, Time= 4h, p= 2585.7Torr Ismaiel; Titeler; Miller; Smith; Glennon; Journal of medicinal chemistry; vol. 33; nb. 2; (1990); p. 755 - 758 View in Reaxys

NH NH

O HN

NH 2

Rx-ID: 3628241 View in Reaxys 29/102 Yield

Conditions & References

82 %

With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH NH

O HN

NH 2

Rx-ID: 3628242 View in Reaxys 30/102 Yield

Conditions & References

82 %

With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH NH

O HN

NH 2

Rx-ID: 3628243 View in Reaxys 31/102 Yield 79 %

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NH NH

O HO

NH 2

Rx-ID: 3628244 View in Reaxys 32/102 Yield

Conditions & References

79 %

With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH HO

NH 2

Rx-ID: 5453005 View in Reaxys 33/102 Yield

Conditions & References 2-Amino-1-<5-benzyloxy-indolyl-(3)>-propan*HCl (in W.), 1. aq. KOH, 2. Hydrierung an Pd/C (in Ae.) Heinzelman et al.; Journal of Organic Chemistry; vol. 25; (1960); p. 1548,1552 View in Reaxys

NH NH

O HO

N O

NH 2

Rx-ID: 18815980 View in Reaxys 34/102 Yield

Conditions & References Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 64 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 82 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 18 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 82 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

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NH NH

O HO

N O

NH 2

Rx-ID: 18815981 View in Reaxys 35/102 Yield

Conditions & References Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 33 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 79 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 37 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 79 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH 2

Rx-ID: 18845226 View in Reaxys 36/102 Yield

Conditions & References Reaction Steps: 2 1: 64 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 82 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 2 1: 18 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 82 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH 2

Rx-ID: 18845227 View in Reaxys 37/102 Yield

Conditions & References Reaction Steps: 2

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1: 33 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 79 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 2 1: 37 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 79 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH HO

N H NH 2

Rx-ID: 41994278 View in Reaxys 38/102 Yield

Conditions & References

58 %

NH HO

N H NH 2

Rx-ID: 41994279 View in Reaxys 39/102 Yield

Conditions & References

48 %

NH F

NH 2

Rx-ID: 5824401 View in Reaxys 40/102 Yield

Conditions & References 5-Fluor-3-(2-nitro-propenyl)-indol, LiAlH4 Kalir,A.; Szara,S.; J. Med. Chem.; vol. 6; (1963); p. 716 - 719 View in Reaxys 5-Fluor-3-(2-amino-propyl)-indol-2-carbonsaeure, wss.HCl, Essigsaeure <Δ> Suworow et al.; J. Gen. Chem. USSR (Engl. Transl.); vol. 33; (1963); p. 3738,3672 View in Reaxys

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5-Fluor-3-hydroxy-3-(2-oximino-propyl)-oxindol, Red. mit LiAlH4, sd. Tetrahydrofuran Franklin; White; Journal of the Chemical Society; (1963); p. 1335,1336 View in Reaxys 5-Fluor-3-hydroxy-3-(2-oximino-propyl)-oxindol in THF, LiAlH4 (20grad, dann Siedetemp., 12 Std.) Franklin; White; Journal of the Chemical Society; (1963); p. 1335,1336 View in Reaxys syn-, anti-3-(4-Fluor-phenylhydrazono)-6-methyl-piperidon-(2) (Gemisch) Suworow et al.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); (1962); p. 679; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; (1962); p. 729 View in Reaxys

F N O

NH 2

Rx-ID: 10387336 View in Reaxys 41/102 Yield

Conditions & References With chloro-trimethyl-silane, borane in tetrahydrofuran, Time= 14h, T= 20 °C Marshall, Daniel R.; Rodriguez, Gus; Thomson, David S.; Nelson, Richard; Capolina, Allison; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 2; (2007); p. 315 - 319 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Reflux Yeung, Bryan K. S.; Zou, Bin; Rottmann, Matthias; Lakshminarayana, Suresh B.; Ang, Shi Hua; Leong, Seh Yong; Tan, Jocelyn; Wong, Josephine; Keller-Maerki, Sonja; Fischli, Christoph; Goh, Anne; Schmitt, Esther K.; Krastel, Philipp; Francotte, Eric; Kuhen, Kelli; Plouffe, David; Henson, Kerstin; Wagner, Trixie; Winzeler, Elizabeth A.; Petersen, Frank; Brun, Reto; Dartois, Veronique; Diagana, Thierry T.; Keller, Thomas H.; Journal of Medicinal Chemistry; vol. 53; nb. 14; (2010); p. 5155 - 5164 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, Reflux Nirogi, Ramakrishna V.S.; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P.; Shinde, Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys General procedure: 1-(5’-Chloroindolyl)-2-nitro-1-butene (0.72 g, 2.8 mmol) was dissolved into anhydrous THF (9 mL). A solution of lithium aluminum hydride (1.0 M/THF, 9 mL, 9 mmol) was added slowly and the reaction was refluxed for 18 h. Upon cooling to room temperature, the reaction mixture was quenched with 1/1 water/THF and then basified to pH 0f 9 with 3.0 N aqueous NaOH solution. The mixture was filtered through Celite and the filtrate was concentrated to 0.73 g of brown oil. The crude material was purified by automated flash chromatography (silica gel, 20percent MeOH/DCM) to yield 0.3 g (47 percent) of colorless oil. This material was dissolved into diethyl ether (25 mL) and a solution of fumaric acid (0.17 g, (1.46 mmol) in MeOH (4 mL) was slowly added. The reaction stirred 18 h at room temperature and the solid product was filtered and recrystallized from MeOH/ethyl ether to yield 180 mg (45percent) of 7e as a white solid; With lithium aluminium tetrahydride in tetrahydrofuran, Time= 18h, Reflux Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.; Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.; Bioorg. Med. Chem. Lett.; vol. 24; nb. 19; (2014); p. 4754 - 4758 View in Reaxys

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F O

NH 2

Rx-ID: 12002000 View in Reaxys 42/102 Yield

Conditions & References Reaction Steps: 2 1: AcOH / 20 °C / sonication 2: BH3; TMSCl / tetrahydrofuran / 14 h / 20 °C With chloro-trimethyl-silane, borane, acetic acid in tetrahydrofuran Marshall, Daniel R.; Rodriguez, Gus; Thomson, David S.; Nelson, Richard; Capolina, Allison; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 2; (2007); p. 315 - 319 View in Reaxys Reaction Steps: 2 1: piperidine; acetic acid / benzene / Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / Reflux With piperidine, lithium aluminium tetrahydride, acetic acid in tetrahydrofuran, benzene Nirogi, Ramakrishna V.S.; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P.; Shinde, Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys Reaction Steps: 2 1: ammonium acetate / 18 h / |Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 18 h / |Reflux With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.; Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.; Bioorg. Med. Chem. Lett.; vol. 24; nb. 19; (2014); p. 4754 - 4758 View in Reaxys

NH NH

F F

NH 2

Rx-ID: 39059066 View in Reaxys 43/102 Yield

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NH NH

O HN

NH 2

Rx-ID: 3627631 View in Reaxys 44/102 Yield

Conditions & References

84 %

With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH NH

O HN

NH 2

Rx-ID: 3627632 View in Reaxys 45/102 Yield

Conditions & References

84 %

With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH NH

O HN

NH 2

Rx-ID: 3627633 View in Reaxys 46/102 Yield

Conditions & References

68 %

With hydrogen, palladium dihydroxide in methanol, Time= 24h, p= 2585.7Torr Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH NH

O HN

NH 2

Rx-ID: 3627634 View in Reaxys 47/102 Yield 68 %

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View in Reaxys

NH O

NH 2

Rx-ID: 5460632 View in Reaxys 48/102 Yield

Conditions & References Oxim V, LiAlH4 Patent; Parke; Davis and Co.; GB974894; (1961); ; vol. 62; nb. 9110a; (1965) View in Reaxys IVa, sd. 10percentig. HCl Terzian et al.; Experientia; vol. 17; (1961); p. 493; vol. 176 View in Reaxys 3-Hydroxy-5-methoxy-3-(2-oximino-propyl), LiAlH4 (in sd. THF) (Red.) Franklin; White; Journal of the Chemical Society; (1963); p. 1335,1336 View in Reaxys Decarboxylierung Patent; Smith; Kline + French Laboratories; US3216898; (1962); ; vol. 64; nb. 3489h; (1966) View in Reaxys 3-Hydroxy-5-methoxy-3-(2-oximino-propyl)-oxindol (in THF), LiAlH4 (erst 20grad, dann 12h Siedetemp.) Franklin; White; Journal of the Chemical Society; (1963); p. 1335,1336 View in Reaxys

(+-)-3-<2-hydroxyimino-propyl>-5-methoxy-indolin-2-one

NH 2

Rx-ID: 5460633 View in Reaxys 49/102 Yield

Conditions & References With propan-1-ol, sodium Pietra; Tacconi; Farmaco, Edizione Scientifica; vol. 13; (1958); p. 893,907 View in Reaxys

5-methoxy-3-<2-nitro-cis(?)-propenyl>-indole

NH 2

Rx-ID: 5460634 View in Reaxys 50/102 Yield

Conditions & References With lithium aluminium tetrahydride, diethyl ether Young; Journal of the Chemical Society; (1958); p. 3493,3494 View in Reaxys

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O N O

NH 2

Rx-ID: 10345483 View in Reaxys 51/102 Yield

O N O

NH 2

Rx-ID: 11189804 View in Reaxys 52/102 Yield

Conditions & References With ammonium formate, palladium on activated charcoal in methanol, Heating Trujillo, John I.; Meyers, Marvin J.; Anderson, David R.; Hegde, Shridhar; Mahoney, Matthew W.; Vernier, William F.; Buchler, Ingrid P.; Wu, Kun K.; Yang, Syaluan; Hartmann, Susan J.; Reitz, David B.; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 16; (2007); p. 4657 - 4663 View in Reaxys

O N NH 2

Rx-ID: 11322595 View in Reaxys 53/102 Yield

Conditions & References Reaction Steps: 2 1: NaOMe; Me2SO4 / methanol / 20 °C 2: HCO2NH4 / Pd/C / methanol / Heating With ammonium formate, sodium methylate, dimethyl sulfate, palladium on activated charcoal in methanol Trujillo, John I.; Meyers, Marvin J.; Anderson, David R.; Hegde, Shridhar; Mahoney, Matthew W.; Vernier, William F.; Buchler, Ingrid P.; Wu, Kun K.; Yang, Syaluan; Hartmann, Susan J.; Reitz, David B.; Bioorganic and Medicinal Chemistry Letters; vol. 17; nb. 16; (2007); p. 4657 - 4663 View in Reaxys

NH O

O O

NH 2

Rx-ID: 12001520 View in Reaxys 54/102

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Yield

NH NH O O N O

NH 2

Rx-ID: 18816119 View in Reaxys 55/102 Yield

Conditions & References Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 50 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 84 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 19 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 84 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

NH NH O O N O

NH 2

Rx-ID: 18816120 View in Reaxys 56/102 Yield

Conditions & References Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 24 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 68 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr

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With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 3 1: 1.) NaOCH3, 2.) aq. TiCl3, aq. AcONH4 / 1) CH3OH, 30 min, room temperature; 2) room temperature, 12 h 2: 36 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 3: 68 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With titanium(III) chloride, ammonium acetate, hydrogen, sodium methylate, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

O O

NH 2

Rx-ID: 18816688 View in Reaxys 57/102 Yield

Conditions & References Reaction Steps: 2 1: 50 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 84 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 2 1: 19 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 84 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys

O O

NH 2

Rx-ID: 18816689 View in Reaxys 58/102 Yield

Conditions & References Reaction Steps: 2 1: 24 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 68 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412 View in Reaxys Reaction Steps: 2 1: 36 percent / NaBH3CN, glacial acetic acid / methanol / 24 h / Ambient temperature; pH 5 - 6 2: 68 percent / H2 / Pd(OH)2/C / methanol / 24 h / 2585.7 Torr With hydrogen, sodium cyanoborohydride, acetic acid, palladium dihydroxide in methanol Nichols; Lloyd; Johnson; Hoffman; Journal of Medicinal Chemistry; vol. 31; nb. 7; (1988); p. 1406 - 1412

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View in Reaxys

NH Cl

NH 2

Rx-ID: 5824402 View in Reaxys 59/102 Yield

Conditions & References 3-(2-Amino-propyl)-5-chlor-indol-2-carbonsaeure, wss.HCl, Essigsaeure <Δ> Suworow et al.; J. Gen. Chem. USSR (Engl. Transl.); vol. 33; (1963); p. 3738,3672 View in Reaxys 1-Methyl-2-<5-chlor-indolenidenium-(3)>-ethylnitronat, LiAlH4 Whittle et al.; Journal of Medicinal Chemistry; vol. 6; (1963); p. 378,380 View in Reaxys Decarboxylierung Patent; Smith; Kline + French Laboratories; US3216898; (1962); ; vol. 64; nb. 3489h; (1966) View in Reaxys entspr. Nitroethen II, LiAlH4 Patent; Imperial Chemical Industries Ltd.; GB982738; (1961); ; vol. 62; nb. 11784h; (1965) View in Reaxys syn-, anti-3-(4-Chlor-phenylhydrazono)-6-methyl-piperidon-(2) (Gemisch) Suworow et al.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); (1962); p. 679; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; (1962); p. 729 View in Reaxys

O N

O Cl

NH 2

Rx-ID: 28800482 View in Reaxys 60/102 Yield 94.9 %

Conditions & References 59 :To a suspension of lithium aluminum hydride (2.62 g, 68.2 mmol) in tetrahydrofuran (70 mL) was added the nitro intermediate (2.69 g, 11.37 mmol) in small portions. The resulting reaction mixture was refluxed at 90° C. for 6 hours. Afterward, the reaction mixture was cooled to room temperature and placed in an ice bath. It was then quenched by adding a water-THF mixture (6:4, 70 mL) slowly, followed by aqueous sodium hydroxide (4 M, 70 mL). The resultant suspension was allowed to stir overnight and was then filtered through celite. The filtrate obtained was concentrated in vacuo, diluted with water and extracted with ethyl acetate. The extracts was washed with water and brine, dried by sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was placed under high vacuum to afford 2-(5-chloro-1H-indol-3-yl)-1-methyl-ethylamine as a brown oil (2.25 g, 94.9percent). 1HNMR (300 MHz, DMSO-d6): δ 11.01 (bs, 1H), 7.55 (d, J=2.05 Hz, 1H), 7.34 (d, J=9.08 Hz, 1H), 7.20 (d, J=1.76 Hz, 1H), 7.04 (dd, J=8.5, 2.1 Hz, 1H), 2.96-3.10 (m, 1H), 2.60 (d, J=6.5 Hz, 2H), 0.97 (d, J=6.5 Hz, 3H); MS (ESI) m/z 208.0 (M+H)+. Stage 1: With lithium aluminium tetrahydride in tetrahydrofuran, T= 90 °C Stage 2: With water, sodium hydroxide in tetrahydrofuran, Cooling with ice Patent; NOVARTIS AG; US2009/275560; (2009); (A1) English View in Reaxys General procedure: 1-(5’-Chloroindolyl)-2-nitro-1-butene (0.72 g, 2.8 mmol) was dissolved into anhydrous THF (9 mL). A solution of lithium aluminum hydride (1.0 M/THF, 9 mL, 9 mmol) was added slowly and the reaction was refluxed for 18 h. Upon cooling to room temperature, the reaction mixture was quenched with 1/1 water/THF and then basified to pH 0f 9 with 3.0 N aqueous NaOH solution. The mixture was filtered through Celite and the filtrate was

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concentrated to 0.73 g of brown oil. The crude material was purified by automated flash chromatography (silica gel, 20percent MeOH/DCM) to yield 0.3 g (47 percent) of colorless oil. This material was dissolved into diethyl ether (25 mL) and a solution of fumaric acid (0.17 g, (1.46 mmol) in MeOH (4 mL) was slowly added. The reaction stirred 18 h at room temperature and the solid product was filtered and recrystallized from MeOH/ethyl ether to yield 180 mg (45percent) of 7e as a white solid; With lithium aluminium tetrahydride in tetrahydrofuran, Time= 18h, Reflux Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.; Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.; Bioorg. Med. Chem. Lett.; vol. 24; nb. 19; (2014); p. 4754 - 4758 View in Reaxys

NH Cl

Cl NH 2

Rx-ID: 39059062 View in Reaxys 61/102 Yield

NH Cl

Cl O

NH 2

Rx-ID: 39059117 View in Reaxys 62/102 Yield

Conditions & References Reaction Steps: 2 1: ammonium acetate / 18 h / |Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 18 h / |Reflux With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.; Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.; Bioorg. Med. Chem. Lett.; vol. 24; nb. 19; (2014); p. 4754 - 4758 View in Reaxys

H 2N

O O

HN HO

Z O

O OH

NH 2 H 2N

Rx-ID: 25045171 View in Reaxys 63/102 Yield

Conditions & References 19.iii : (ii) (iii) 3-(2-Aminopropyl)-1H-indole-5-carboxamide, compound with maleic acid and water (2:2:1) A mixture of 3[(2-methyl-2-nitro)ethyl]-1H-indole-5-carboxamide (1 g), Raney nickel (1 g) and ethanol (100 ml) was stirred in a hydrogen atmosphere for 3 hours. The reaction mixture was filtered and the filtrate was concentrated to about 25 ml.

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A solution of maleic acid (0.5 g) in ethanol (25 ml) was added and after 0.2 hours the solution was diluted with ether (150 ml). Repeated trituration of the resulting gum with dry ether gave a light brown solid which was filtered off and dried to give the title compound (0.68 g) m.p. 180°-4° C. Analysis Found: C, 56.3; H, 5.95; N, 11.9percent, C12 H15 N3 O.C4 H4 O4.1/2H 2 O requires: C, 56.15; H, 5.85; N, 12.25percent. With nickel monoaluminide in ethanol Patent; Glaxo Group Limited; US4252803; (1981); (A1) English View in Reaxys

NH HO O NH 2

Rx-ID: 5609904 View in Reaxys 64/102 Yield

Conditions & References Hydrazid (III, R=Me, R'=H), HCl Terzyan et al.; Izvestiya Akademii Nauk Armyanskoi SSR, Khimicheskie Nauki; vol. 18; nb. 1; (1965); p. 88,89-91; ; vol. 63; nb. 6948e; (1965) View in Reaxys O N

NH 2

Rx-ID: 33659926 View in Reaxys 65/102 Yield

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, Reflux Nirogi, Ramakrishna V.S.; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P.; Shinde, Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys NH 2 NH

O O O

Rx-ID: 33659958 View in Reaxys 66/102 Yield

Conditions & References Reaction Steps: 2 1: piperidine; acetic acid / benzene / Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / Reflux With piperidine, lithium aluminium tetrahydride, acetic acid in tetrahydrofuran, benzene Nirogi, Ramakrishna V.S.; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P.; Shinde, Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys

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NH S

NH 2

Rx-ID: 5599372 View in Reaxys 67/102 Yield

Conditions & References 3-(2-Amino-propyl)-5-methylmercapto-indol-2-carbonsaeure (in Eg./aq. HCl), Δ Horner,J.K. et al.; Canadian Journal of Chemistry; vol. 44; (1966); p. 307 - 313 View in Reaxys

O HO

0.5HO

NH 2 OH N H

NH 2

Rx-ID: 39059050 View in Reaxys 68/102 Yield

Conditions & References Preparation of2-Amino-1-(5’-Chloro-(3-Indolyl))butane (0.5 fumarate) (7e). General procedure: 1-(5’-Chloroindolyl)-2-nitro-1-butene (0.72 g, 2.8 mmol) was dissolved into anhydrous THF (9 mL). A solution of lithium aluminum hydride (1.0 M/THF, 9 mL, 9 mmol) was added slowly and the reaction was refluxed for 18 h. Upon cooling to room temperature, the reaction mixture was quenched with 1/1 water/THF and then basified to pH 0f 9 with 3.0 N aqueous NaOH solution. The mixture was filtered through Celite and the filtrate was concentrated to 0.73 g of brown oil. The crude material was purified by automated flash chromatography (silica gel, 20percent MeOH/DCM) to yield 0.3 g (47 percent) of colorless oil. This material was dissolved into diethyl ether (25 mL) and a solution of fumaric acid (0.17 g, (1.46 mmol) in MeOH (4 mL) was slowly added. The reaction stirred 18 h at room temperature and the solid product was filtered and recrystallized from MeOH/ethyl ether to yield 180 mg (45percent) of 7e as a white solid; in methanol, diethyl ether, Time= 18h, T= 20 °C Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.; Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.; Bioorg. Med. Chem. Lett.; vol. 24; nb. 19; (2014); p. 4754 - 4758 View in Reaxys

NH 2 N H

H 2N

Rx-ID: 25144975 View in Reaxys 69/102 Yield

Conditions & References The method of claim 1, wherein said compound is ... N-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]urea, N-[3-(2-methylaminoethyl)-1H-indol-5-yl]urea, N-[3-(2-methylethylaminoethyl)-1H-indol-5-yl]urea, N-[3-{2-[N-(1-methyl-2-pyrrolidinylidene)]ethylamine}-1H-indol-5-yl]urea, N-[3(2-aminopropyl)-1H-indol-5-yl]urea, N-[3-(2-aminoethyl)-1-methyl-1H-indol-5-yl]urea, or N-[3-(2-aminoethyl)-6-chloro-1H-indol-5-yl]urea, Patent; McNeilab, Inc.; US4803218; (1989); (A1) English View in Reaxys

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O N

NH 2

Rx-ID: 33659928 View in Reaxys 70/102 Yield

O O

Rx-ID: 33659959 View in Reaxys 71/102 Yield

F O

NH 2

Rx-ID: 1777557 View in Reaxys 72/102 Yield

Conditions & References in various solvent(s), Time= 142h, T= 45 °C , protease subtilisin Carlsberg, Yield given Kitaguchi, Hiroshi; Fitzpatrick, Paul A.; Huber, Joel E.; Klibanov, Alexander M.; Journal of the American Chemical Society; vol. 111; nb. 8; (1989); p. 3094 - 3095 View in Reaxys

F O

NH 2

Rx-ID: 4720213 View in Reaxys 73/102

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Yield

Conditions & References With subtilisin-CLEC in various solvent(s), T= 40 °C , Yield given. Yields of byproduct given. Title compound not separated from byproducts Wang, Yi-Fong; Yakovlevsky, Kirill; Zhang, Bailing; Margolin, Alexey L.; Journal of Organic Chemistry; vol. 62; nb. 11; (1997); p. 3488 - 3495 View in Reaxys

NH 2

Rx-ID: 4720215 View in Reaxys 74/102 Yield

Conditions & References Yield given. Yields of byproduct given Wang, Yi-Fong; Yakovlevsky, Kirill; Zhang, Bailing; Margolin, Alexey L.; Journal of Organic Chemistry; vol. 62; nb. 11; (1997); p. 3488 - 3495 View in Reaxys

NH HN

NH 2

Rx-ID: 30558142 View in Reaxys 75/102 Yield

Conditions & References Reaction Steps: 3 1: ammonium acetate / 6 h / Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / Inert atmosphere; Reflux 3: lipase B from Candida antarctica / tetrahydrofuran / 3.5 h / 30 °C / Inert atmosphere; Enzymatic reaction With lithium aluminium tetrahydride, ammonium acetate in tetrahydrofuran, 1: Henry reaction Rodriguez-Mata, Maria; Gotor-Fernandez, Vicente; Gonzalez-Sabin, Javier; Rebolledo, Francisca; Gotor, Vicente; Organic and Biomolecular Chemistry; vol. 9; nb. 7; (2011); p. 2274 - 2278 View in Reaxys

NH 2

Rx-ID: 30558147 View in Reaxys 76/102 Yield 88 %, 81 %

Conditions & References With lipase B from Candida antarctica in tetrahydrofuran, Time= 3.5h, T= 30 °C , Inert atmosphere, Enzymatic reaction, optical yield given as percent ee Rodriguez-Mata, Maria; Gotor-Fernandez, Vicente; Gonzalez-Sabin, Javier; Rebolledo, Francisca; Gotor, Vicente; Organic and Biomolecular Chemistry; vol. 9; nb. 7; (2011); p. 2274 - 2278 View in Reaxys

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O HN

E N O

NH 2

Rx-ID: 30558151 View in Reaxys 77/102 Yield

Conditions & References Reaction Steps: 2 1: lithium aluminium tetrahydride / tetrahydrofuran / 12 h / Inert atmosphere; Reflux 2: lipase B from Candida antarctica / tetrahydrofuran / 3.5 h / 30 °C / Inert atmosphere; Enzymatic reaction With lithium aluminium tetrahydride in tetrahydrofuran Rodriguez-Mata, Maria; Gotor-Fernandez, Vicente; Gonzalez-Sabin, Javier; Rebolledo, Francisca; Gotor, Vicente; Organic and Biomolecular Chemistry; vol. 9; nb. 7; (2011); p. 2274 - 2278 View in Reaxys

O HO

E O

0.5HO

NH 2

OH N H

NH 2

Rx-ID: 39059052 View in Reaxys 78/102 Yield

NH Br

NH 2

Rx-ID: 5824403 View in Reaxys 79/102 Yield

Conditions & References 5-Brom-3-(2-nitro-prop-1-en-1-yl)-indol, LiAlH4/sd.THF deStevens,G. et al.; Journal of Organic Chemistry; vol. 27; (1962); p. 2457 - 2462 View in Reaxys 3-(2-Amino-propyl)-5-brom-indol-2-carbonsaeure, wss.HCl, Essigsaeure <Δ> Suworow et al.; J. Gen. Chem. USSR (Engl. Transl.); vol. 33; (1963); p. 3738,3672 View in Reaxys syn-, anti-3-(4-Brom-phenylhydrazono)-6-methyl-piperidon-(2) (Gemisch)

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Suworow et al.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); (1962); p. 679; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; (1962); p. 729 View in Reaxys

NH Br

Br O

NH 2

Rx-ID: 33659870 View in Reaxys 80/102 Yield

Br N O

NH 2

Rx-ID: 33659932 View in Reaxys 81/102 Yield

O HO

E O

0.5HO

NH 2

OH N H

NH 2

Rx-ID: 39059051 View in Reaxys 82/102 Yield

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View in Reaxys

O S O

N H NH 2

Rx-ID: 5619804 View in Reaxys 83/102 Yield

Conditions & References Ar-CH=C(Me)-NO2, LiAlH4 Patent; Mead Johnson; US3472870; (1969); ; vol. 72; nb. 66816 View in Reaxys

NH O

NH 2

Rx-ID: 5518771 View in Reaxys 84/102 Yield

Conditions & References Indol V, LiAlH4 Patent; Upjohn Co.; GB886684; (1962); ; vol. 57; nb. 7234g; (1962) View in Reaxys entspr. Nitroverb., LiAlH4 Patent; Upjohn; US3168526; (1965); ; vol. 62; nb. 16200d; (1965) View in Reaxys 2-Nitro-1-<5-benzyloxy-indolyl-(3)>-propan, LiAlH4 (in Ae.) Heinzelman et al.; Journal of Organic Chemistry; vol. 25; (1960); p. 1548,1552 View in Reaxys

5-benzyloxy-3-<2-nitro-cis(?)-propenyl>-indole

<5-benzyloxy-indol-3-yl>-methanol

NH 2

Rx-ID: 5723849 View in Reaxys 85/102 Yield

Conditions & References With tetrahydrofuran, lithium aluminium tetrahydride Ash; Wragg; Journal of the Chemical Society; (1958); p. 3887,3892 View in Reaxys O N

NH O

NH 2

Rx-ID: 33659927 View in Reaxys 86/102 Yield

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Anil K.; Deshpande, Amol D.; Dwarampudi, Adireddy; Chindhe, Anil K.; Dubey, Pramod Kumar; Journal of Enzyme Inhibition and Medicinal Chemistry; vol. 27; nb. 3; (2012); p. 443 - 450 View in Reaxys

NH O

O NH 2

Rx-ID: 33659943 View in Reaxys 87/102 Yield

O NH

Rx-ID: 33659914 View in Reaxys 88/102 Yield

NH 2

O NH

Rx-ID: 33659929 View in Reaxys 89/102 Yield

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NH HO

Z O

HO O

OH NH 2

Rx-ID: 8212957 View in Reaxys 90/102 Yield

Conditions & References 3-(2-Nitropropyl)-5-benzyloxyindol, H2, Maleinsaeure Patent; Warner-Lambert Pharm.Co.; US3037031; (1962); ; vol. 57; nb. 12439e; (1962) View in Reaxys

HN HN S O O

HCl

H 2N

Rx-ID: 24842041 View in Reaxys 91/102 Yield

Conditions & References 7.iv : (iv) A solution of the oil in ethanol (5 ml) was treated with ethereal hydrogen chloride (pH 3), the salt filtered off and dried to give the title compound as a solid (0.2 g) m.p. 211°-212°. Analysis Found: C,50.4;H,6.7;N,12.2 C14 H21 N3 O2 S.HCl.O.18H2 O requires C,50.2;H,6.7;N,12.5. Patent; Glaxo Group Limited; US4994483; (1991); (A1) English View in Reaxys

O HO

NH 2 N H

O H 2N

Rx-ID: 25144970 View in Reaxys 92/102 Yield 1.63 g (64%)

Conditions & References 12 : N-[3-(2-Aminopropyl)-1H-indol-5-yl]urea (E)-2-Butenedioate (2:1) Hydrate (10:1) EXAMPLE 12 N-[3-(2-Aminopropyl)-1H-indol-5-yl]urea (E)-2-Butenedioate (2:1) Hydrate (10:1) 5-Nitro-3-(2-nitropropyl)indole: To a solution of 0.3 g (0.013 mole) of Na in 65 ml of abs EtOH was added 2.93 g (0.039 mole) of nitroethane dropwise. To the white suspension was added 2.19 g (0.01 mole) of 5-nitrogramine suspended in 40 ml of abs EtOH, followed by 2.5 g (0.02 mole) of dimethylsulfate in 20 ml of abs EtOH dropwise over 15 minutes. The mixture was stirred for 2 hours, then poured into 350 ml of ice water. The yellow solid was filtered, washed with ice water and air-dried to give 1.63 g (64percent) of product: m.p. 130-131.5. Anal. Calcd for C11 H11 N3 O4:C, 53.01; H, 4.45; N, 16.86. Found: C, 53.06; H, 4.55; N, 16.66. Patent; McNeilab, Inc.; US4803218; (1989); (A1) English View in Reaxys

NH O

N O

NH 2 HN

O OH

NH 2 N H

H 2N

Rx-ID: 25193161 View in Reaxys 93/102 Yield

Conditions & References 12 : N-[3-(2-Aminopropyl)-indol-1H-5-yl]urea (E)-2-Butenedioate (2:1) Hydrate (10:1):

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N-[3-(2-Aminopropyl)-indol-1H-5-yl]urea (E)-2-Butenedioate (2:1) Hydrate (10:1): A solution of 3.8 g (0.015 mole) of N-[3-(2-nitropropyl)-1H-indol-5-yl]urea in 200 ml of abs EtOH saturated with NH3 was treated with one spoonful of activated RaNi and hydrogenated for 2 hours. The catalyst was removed by filtration and solvents removed in vacuo to give a beige solid; 2.6 g (79percent crude yield). This crude product was purified by dry column chromatography (3percent NH4 OH-MeOH/silica gel) to give 2.0 g of product, which was dissolved in 190 ml of i-PrOH and treated with 0.94 g of fumaric acid in i-PrOH. The immediate precipitate was filtered and solvent removed in vacuo to give a goo which on heating with minimal iPrOH affords a white precipitate. Filtration and recrystallization twice from H2 O affords 0.51 g of pure desired product: m p. 236°-238°; i.r. (KBr) 3375, 3160, 1650-1700 (broad), and 1520 cm-1; nmr (d6 -DMSO) δ(TMS) 10.72 (1, S, indole--NH), 8.66 (1, S, --NHCO--), 7.51 (1,S), 7.21 (1, d, Jortho =8 Hz), 7.19 (1, S, indole C2 -H), 7.13 (1, d of d, Jortho =8 Hz, Jmeta =2 Hz, 6.48 (1, S, =CHCO2 H), 5.81 (2, S, NH2 CO--), 5.54 (broad S, --NH3), 3.3 (1, m), 2.85 (2, m, d of d) and 1.08 ppm (3, d, J=7 Hz). Anal. Calcd for C12 H16 N4 O.1/2 H2 O: C, 57.56; H, 6.29; N, 19.18; H2 O, 0.62. Found: C, 57.69; H, 6.35; N, 19.06; H2 O, 0.84. With ammonia in abs EtOH, isopropyl alcohol Patent; McNeilab, Inc.; US4803218; (1989); (A1) English View in Reaxys

O O

NH 2

Rx-ID: 4495432 View in Reaxys 94/102 Yield 78 %

Conditions & References With hydrogenchloride in ethyl acetate, Time= 2h Glennon, Richard A.; Hong, Seoung-Soo; Bondarev, Mikhail; Law, Ho; Dukat, Malgorzata; Rakhit, Suman; Power, Patricia; Fan, Ermei; Kinneau, Diana; Kamboj, Rajender; Teitler, Milt; Herrick-Davis, Katharine; Smith, Carol; Journal of Medicinal Chemistry; vol. 39; nb. 1; (1996); p. 314 - 322 View in Reaxys

NH O

NH 2

Rx-ID: 17751347 View in Reaxys 95/102 Yield

Conditions & References Reaction Steps: 2 1: 62 percent / K2CO3 / acetonitrile / 24 h / Heating 2: 78 percent / HCl / ethyl acetate / 2 h With hydrogenchloride, potassium carbonate in ethyl acetate, acetonitrile Glennon, Richard A.; Hong, Seoung-Soo; Bondarev, Mikhail; Law, Ho; Dukat, Malgorzata; Rakhit, Suman; Power, Patricia; Fan, Ermei; Kinneau, Diana; Kamboj, Rajender; Teitler, Milt; Herrick-Davis, Katharine; Smith, Carol; Journal of Medicinal Chemistry; vol. 39; nb. 1; (1996); p. 314 - 322 View in Reaxys

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NH 2

Rx-ID: 17756048 View in Reaxys 96/102 Yield

Conditions & References Reaction Steps: 4 1: 88 percent / ethyl acetate / 24 h / Ambient temperature 2: 76 percent / H2 / 10percent Pd/C / methanol / 12 h / 2068.6 Torr 3: 62 percent / K2CO3 / acetonitrile / 24 h / Heating 4: 78 percent / HCl / ethyl acetate / 2 h With hydrogenchloride, hydrogen, potassium carbonate, palladium on activated charcoal in methanol, ethyl acetate, acetonitrile Glennon, Richard A.; Hong, Seoung-Soo; Bondarev, Mikhail; Law, Ho; Dukat, Malgorzata; Rakhit, Suman; Power, Patricia; Fan, Ermei; Kinneau, Diana; Kamboj, Rajender; Teitler, Milt; Herrick-Davis, Katharine; Smith, Carol; Journal of Medicinal Chemistry; vol. 39; nb. 1; (1996); p. 314 - 322 View in Reaxys

NH NH

HO O

NH 2

Rx-ID: 17776576 View in Reaxys 97/102 Yield

HN O

NH 2

Rx-ID: 17780502 View in Reaxys 98/102 Yield

Conditions & References Reaction Steps: 3 1: 76 percent / H2 / 10percent Pd/C / methanol / 12 h / 2068.6 Torr 2: 62 percent / K2CO3 / acetonitrile / 24 h / Heating 3: 78 percent / HCl / ethyl acetate / 2 h With hydrogenchloride, hydrogen, potassium carbonate, palladium on activated charcoal in methanol, ethyl acetate, acetonitrile Glennon, Richard A.; Hong, Seoung-Soo; Bondarev, Mikhail; Law, Ho; Dukat, Malgorzata; Rakhit, Suman; Power, Patricia; Fan, Ermei; Kinneau, Diana; Kamboj, Rajender; Teitler, Milt; Herrick-Davis, Katharine; Smith, Carol; Journal of Medicinal Chemistry; vol. 39; nb. 1; (1996); p. 314 - 322 View in Reaxys

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F N H

F F

NH 2

O HN

NH O

NH 2

Rx-ID: 28781424 View in Reaxys 99/102 Yield

Conditions & References

51 %

With Alkaline protease in 3-methyl pentan-3-ol, Time= 6h, T= 20 °C , Enzymatic reaction, optical yield given as percent ee Nechab, Malek; El Blidi, Lahssen; Vanthuyne, Nicolas; Gastaldi, Stephane; Bertrand, Michele P.; Gil, Gerard; Organic and Biomolecular Chemistry; vol. 6; nb. 21; (2008); p. 3917 - 3920 View in Reaxys

O F

N H

NH 2

H N

N H

NH 2

Rx-ID: 33556067 View in Reaxys 100/102 Yield

Conditions & References

46 %, 53 %

With coated protease in 3-methyl pentan-3-ol, Time= 192h, T= 21 °C , Resolution of racemate, Enzymatic reaction, enantioselective reaction Queyroy, Severine; Vanthuyne, Nicolas; Gastaldi, Stephane; Bertrand, Michele P.; Gil, Gerard; Advanced Synthesis and Catalysis; vol. 354; nb. 9; (2012); p. 1759 - 1764 View in Reaxys

HN H N E O

S O

O H N O 2

N H

OHHO O

O S

N O

Rx-ID: 25034154 View in Reaxys 101/102 Yield

Conditions & References 16.iii : (iii) (iii) N-[[3-(2-Aminopropyl)-1H-indol-5-yl]methyl]methanesulphonamide, maleate A solution of N-[[3-(2-nitro-1-propenyl)-1H-indol-5-yl]methyl]methanesulphonamide (0.6 g) in dry tetrahydrofuran (30 ml) was added dropwise over 15 min, under nitrogen to a stirred suspension of lithium aluminium hydride (0.6 g) in dry tetrahydrofuran (30 ml). The mixture was heated to reflux with stirring for 5 h and then cooled in ice. Aqueous tetrahydrofuran (15percent H2 O; 20 ml) was added dropwise followed by water (40 ml) and ethyl acetate (20 ml). The mixture was saturated with solid sodium chloride and filtered. The two phase filtrate was separated and the aqueous phase was extracted with ethyl acetate (2*50 ml). The combined extracts were dried (Na2 SO4) and evaporated to give a colourless gum (0.62 g).

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A portion of this gum (0.5 g) was dissolved in hot methanol (ca 3 ml) and a solution of maleic acid (0.21 g) in hot methanol (ca 1 ml) was added. On diluting with dry ether (ca 15 ml) and cooling a brown oil precipitated, which was triturated with dry ether (3*20 ml). Crystallisation of the resulting brown solid (0.45 g) from methanol (ca 4 ml) and ether (ca 14 ml) over 3 days gave the title maleate as a brown solid (0.27 g) m.p. 140°-142°. Analysis Found: C, 51.5; H, 5.8; N, 10.6; C13 H19 N3 O2 S.C4 H4 O4 requires: C, 51.4; H, 5.8; N, 10.5percent. in tetrahydrofuran, methanol, water, ethyl acetate Patent; Glaxo Group Limited; US4636521; (1987); (A1) English View in Reaxys H 2N OH

(+-)-2-<5-benzyloxy-indol-3-yl>-1-methyl-ethylamine sulfate

HO NH

S OO

Rx-ID: 8423047 View in Reaxys 102/102 Yield

Conditions & References With palladium on activated charcoal, ethanol, Hydration Ash; Wragg; Journal of the Chemical Society; (1958); p. 3887,3892 View in Reaxys

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